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Patients started on pyrazinamide should have baseline serum uric acid and liver function determinations. Those patients with preexisting Iiver disease or those at increased risk for drug related hepatitis (e.g., alcohol abusers) should be followed closely.
Pyrazinamide should be discontinued and not be resumed if signs of hepatocel-lular damage or hyperuricemia accompanied by an acute gouty arthritis appear.
Pyrazinamide inhibits renal excretion of urates, frequently resulting in hyperuricemia which is usually asymptomatic. If hyperuricemia is accompanied by acute gouty arthritis, pyrazinamide should be discontinued.
Pyrazinamide should be used with caution in patients with a history of diabetes mellitus, as management may be more difficult.
Primary resistance of M. tuberculosisto pyrazinamide is uncommon. In cases with known or suspected drug resistance, in vitro susceptibility tests with recent cultures of M. tuberculosis against pyrazinamide and the usual primary drugs should be performed. There are few reliable in vitro tests for pyrazinamide resistance. A reference laboratory capable of performing these studies must be employed.
Baseline liver function studies [especially ALT (SGPT), AST (SGOT) determinations] and uric acid levels should be determined prior to therapy. Appropriate laboratory testing should be performed at periodic intervals and if any clinical signs of symptoms occur during therapy.
Carcinogenicity, Mutagenicity, Impairment of Fertility
6,7,8 In lifetime bioas-says in rats and mice, pyrazinamide was administered in the diet at concentrations of up to 10,000 ppm. This resulted in estimated daily doses for the mouse of 2 g/kg, or 40 times the maximum human dose, and for the rat of 0.5 g/kg, or 10 times the maximum human dose. Pyrazinamide was not carcinogenic in rats or male mice and no conclusion was possible for female mice due to insufficient numbers of surviving control mice.
Pyrazinamide was not mutagenic in the Ames bacterial test, but induced chro-mosomal aberrations in human Iymphocyte cell cultures.
Teratogenic Effects - Pregnancy Category C Animal reproduction studies have not been conducted with pyrazinamide. It is also not known whether pyrazinamide can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Pyrazinamide should be given to a pregnant woman only if clearly needed.
Pyrazinamide has been found in small amounts in breast milk. Therefore, it is advised that pyrazinamide be used with caution in nursing mothers taking into account the risk-benefit of this therapy.9
Pyrazinamide regimens employed in adults are probably equally effective in pediatric patients.4,10,11 Pyrazinamide appears to be well tolerated in pediatric patients.
12 Clinical studies of pyrazinamide did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic or renal function, and of concomitant disease or other drug therapy.
It does not appear that patients with impaired renal function require a reduction in dose. It may be prudent to select doses at the low end of the dosing range, however.13
4. Treatment of tuberculosis and tuberculosis infection in adults and children. Am Rev Respir Dis. 1986 ; 134 : 363-368.
5. Reynolds JEF, Parfitt K, Parsons AV, Sweetman SC. Martindale The Extra Pharmacopoeia, ed 29. London, The Pharmaceutical Press. 1989; 569-570.
6. Bioassay of pyrazinamide for possible carcinogenicity. National Cancer Institute Carcinogenesis Technical Report Series No. 48, 1978.
7. Zerger E, Anderson B, Haworth S, Lawlor T, Mortelmans K, Speck W. Salmonella mutagenicity tests: III. Results from the testing of 255 chemicals. Environ Mutagen. 1987; 9 (Suppl 9) : 1-109.
8. Roman IC, Georgian L. Cytogenetic effects of some antituberculosis drugs in vitro. Mutation Research. 1977; 48: 215-224.
9. Holdiness M. Antituberculosis drugs and breast-feeding. Arch Intern Med. 1984 ; 144 : 1888.
10. Turcios N, Evans H. Preventing and managing tuberculosis in children. J Resp Dis. 1989 ; 10 (6) (Jun): 23.
11. Starke JR. Multidrug therapy for tuberculosis in children. Pediatr Infec Dis J. 1990 ; 9: 785-793.
12. Specific requirements on content and format of labeling for human prescription drugs; proposed addition of “geriatric use” subsection in the labeling. Federal Register. 1990 ; 55 (212) (Nov 1): 46134-46137.
13. Stamathakis G, Montes C, Trouvin JH, et al. Pyrazinamide and pyrazinoic acid pharmacokinetics in patients with chronic renal failure. Clinical Nephrology. 1988 ; 30 : 230-234.This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 12/3/2008
Additional Pyrazinamide Information
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